This Week in PLOS Medicine: AIDS Treatment in Children, Influenza Vaccination Strategies, Patient Safety, and Antimicrobial Resistance in China

This week PLOS Medicine publishes the following new articles:

Image credit: NIAID

Image credit: NIAID, Flickr

Using observational data collected in cohort studies in Southern Africa, Michael Schomaker and colleagues estimate the mortality associated with starting Antiretroviral Therapy (ART) at different CD4 thresholds among children aged 2–5 years. Recent changes to World Health Organization guidelines for starting anti-AIDS drugs in young children are unlikely to improve death rates but may increase the numbers of children receiving ART by simplifying access to treatment. The findings suggest that, among southern African children aged 2–5 years at HIV diagnosis, there was no difference in three year death rates between children in whom ART was started immediately and those in whom starting ART was deferred until their CD4 count and percentage (markers of progression of HIV infection) fell below 750 cells/mm3 and 25% respectively.
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Battling Viral Hemorrhagic Fever in Southwest Uganda

In the second of two linked posts Raquel Reyes from Massachusetts General Hospital describes the challenges of providing health care during viral hemorrhagic fever outbreaks in Southwest Uganda.

On October 19th 2012, two weeks after Uganda was officially declared Ebola-free, the Ministry of Health declared an outbreak of Marburg virus. Like Ebola, Marburg virus is in the filovirus family. Like Ebola, Marburg causes a viral hemorrhagic fever (VHF). It is spread in infected body fluids, is highly virulent, and carries a case-fatality rate of between about 25 to 80%. For all intents and purposes, Marburg and Ebola are the same.

Having only recently dealt with an Ebola outbreak that started shortly after my arrival in Uganda, it was easier to mobilize our task force and begin the work of setting up the isolation camp. There was greater urgency, as well – a pregnant woman at our hospital in Mbarara had died within 24 hours of admission, and her blood test returned positive for Marburg. A post-mortem caesarean section was performed to remove the fetus according to local custom.  Not appreciating the danger, the deceased patient’s husband took the bodies back to his village to prepare for burial—one of the highest risk opportunities for viral spread.

Decontaminating health workers as they leave the isolation ward. Image Credit: Raquel Reyes.

Decontaminating health workers as they leave the isolation ward. Image Credit: Raquel Reyes.


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July 28, 2012: “Emergency Message – Confirmed Case Of Ebola Virus In Uganda”

In the first of two linked posts Raquel Reyes from Massachusetts General Hospital describes the challenges of providing health care during viral hemorrhagic fever outbreaks in Southwest Uganda.

To read the second of these linked posts, please click here.

Preparing for an Ebola outbreak. Image Credit: Raquel Reyes.

Shortly after my arrival to Uganda in July 2012, I received an email with the subject heading “Emergency Message – Confirmed Case Of Ebola Virus In Uganda”. I was taken aback. Earlier in the day, one of the lead physicians in the Department of Internal Medicine at Mbarara Regional Referral Hospital had shown me the small area used for isolation during the last major Ebola outbreak in 2007, now used to house patients with TB. It was a small area near the back of the hospital with a six-room building and a few wooden sheltered areas with tin roofing. That evening, still before receiving the alert, I had written to family and friends about how strange it was to see the isolation ward and posters describing signs and symptoms of Ebola hanging on the walls of the clinics I had visited.

I remember when I first learned about Ebola as a child. It was a strange illness with no cure that made people very sick very quickly, and before people died, they would bleed. It seemed like such a frightening and horrible disease, but foreign and far away. Like the famine in Ethiopia and the earliest reports of HIV/AIDS, it was one of the news stories about Africa that really struck me as a child.  The Ebola virus was first recognized in 1976, the year I was born. More than thirty years later, now a doctor, I found myself in Mbarara, Uganda, working in health facilities that, among many other things, provide food for severely malnourished children and life-saving drugs for patients with HIV. And I find myself reading an email warning of an Ebola outbreak: “On July 27, 2012, local Ugandan press reported 12 deaths due to a “strange illness.”  Laboratory tests conducted by the Uganda Virus Research Institute and the United States Centers for Disease Control and Prevention (CDC) have confirmed, to date, that at least one victim was infected with the Ebola virus.”
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This Week in PLOS Medicine: Endometrial Cancer Development, Respiratory Syncytial Virus Diagnosis in Infants, and Patient Care Improvement

This week PLOS Medicine publishes the following new articles:

Image Credit: Widschwendter et al.

Image Credit: Widschwendter et al.

Martin Widschwendter and colleagues perform an epigenome-wide methylation analysis of endometrial cancers and identify methylation of HAND2 as one of the most common hypermethylated and silenced genes in endometrial cancer. Endometrial cancer is the most common gynecological cancer, and its incidence is continuing to rise in an older and more obese population. HAND2 is active in the healthy endometrium (the tissue lining the uterus) where it antagonizes the growth-inducing effects of estrogen. By contrast, in more than 90% of endometrial cancers, the gene has undergone hypermethylation, an epigenetic modification that doesn’t change its DNA sequence but renders it inactive. Moreover, analysis of HAND2 methylation in endometrial secretions collected from women with postmenopausal bleeding (which can be a symptom of endometrial cancer) accurately identified individuals with early stage cancer.
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TB Patients Take the Stage: Now for an R&D Model That Meets Their Needs

Grania Brigden, TB advisor to the MSF Campaign for Access to Essential Medicines, describes how the current drug R&D model is failing TB patients.

At last week’s Union World Conference on Lung Health, TB patients finally took centre stage, with patients invited to describe the realities of the 2-year treatment regimen for MDR-TB and advocacy groups storming events to call for greater vision in TB treatment and research. Their stories and concerns mirrored those shared with Médecins Sans Frontières (MSF) in a manifesto for better treatment for drug-resistant TB and in blogs by MDR-TB patients.

Patients are right to be concerned. In the past year, there has been no improvement in WHO estimates for MDR-TB: fewer than a third of patients were detected; 170,000 people died; 17,000 patients were diagnosed but not started on treatment; and only 48% of those started on treatment were cured.

 

Zeros Action at Stop TB Symposium from Treatment Action Group
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This Week in PLOS NTDs and PLOS Pathogens: How IT Can Benefit NTDs Control, Type 1 Interferon’s Protection Mechanism, the Improbable Transmission of T. cruzi to Humans, and More

The following new articles are publishing this week in PLOS NTDs:

Andrianaivoarimanana V, Kreppel K, Elissa N, Duplantier J-M, Carniel E, et al. (2013). PLoS Negl Trop Dis 7(11): e2382. doi:10.1371/journal.pntd.0002382

Andrianaivoarimanana V, Kreppel K, Elissa N, Duplantier J-M, Carniel E, et al. (2013). PLoS Negl Trop Dis 7(11): e2382. doi:10.1371/journal.pntd.0002382

In resource-limited settings, the use of IT in healthcare is emerging as it has in recent decades in the West, and a number of efforts are focusing on the use of IT in the control of NTDs. But IT efforts in NTDs lack critical components to maximize human interaction, which is the basis of recent progress in the broader IT community. In this paper, Rajesh Gupta and Paul Wise explore how specific IT products and efforts in the private sector could be adapted for control of NTDs.

Like malaria and dengue, Chagas is transmitted by blood-feeding insects; but unlike those diseases its transmission is through the insects’ feces, not injection into the blood stream. This inefficient process makes estimating the probability of infection difficult. Using mathematical models integrating data on vectors and humans collected across Latin America, Pierre Nouvellet, Eric Dumonteil and Sébastien Gourbière estimated that, for several vector species, transmission occurs in 1 over 900-4000 contacts with infected insects.
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This Week in PLOS Medicine: Global Burden of Depression, Syphilis Treatment in Pregnancy, Response to Measles Outbreaks, & Maternal Rights

This week PLOS Medicine publishes the following new articles:

Nov_5_SoM_thumb

Image Credit: Christian Guthier, Flickr

In their research article, Ferrari and colleagues report the most recent and comprehensive estimates on how much death and disability is attributable to depression, both world-wide and in individual countries and regions. The rates among all causes of disability are highest in Afghanistan and lowest in Japan, and depression ranks first in Central America and Central and Southeast Asia. Disability from depression affects mostly people in their working years, and women more than men. When compared to other diseases and injuries, major depressive disorder (MDD) ranked as the second leading cause of global disability (or YLDs) and the eleventh leading cause of global burden (or DALYs) in 2010. However, MDD also contributes to mortality for a number of other conditions, namely suicide and ischemic heart disease.

Yukari Manabe and colleagues evaluate the cost-effectiveness and budget impact of antenatal syphilis screening for 43 countries in sub-Saharan Africa and estimate the impact of universal screening on averted stillbirths, neonatal deaths, congenital syphilis, and disability-adjusted life years (DALYs). In sub-Saharan Africa, where it is estimated that up to 17% of pregnant women are infected and risk passing the bacterium to their fetus, current screening only achieves 40% coverage. They found that at current syphilis prevalence rates, the intervention could prevent up to 25,000 newborn deaths of and 64,000 stillbirths in sub-Saharan Africa every year. Importantly, although estimated costs varied between countries, on average the cost of each DALY averted was only $11, much less than interventions to prevent mother-to-child transmission of HIV. The authors suggest that an integrated approach to the prevention of mother-to-child transmission of HIV and syphilis combined, as has been introduced in Asia and South America, might further improve cost-efficiency.
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Urgency Needed in the Global Response to Drug-resistant Tuberculosis

In the second of two linked posts, Lindsay McKenna and Colleen Daniels of Treatment Action Group (TAG) describe the importance of access to timely diagnosis and appropriate treatment for patients with drug-resistant tuberculosis and demand that urgency be returned to the global DR-TB response.

“Drs. Dalene and Arne von Delft” the second short film in the series Tuberculosis: Behind the Numbers commissioned by TAG and directed by Jonathan Smith, highlights a young, brave, South African doctor’s two-year battle with multidrug-resistant tuberculosis (MDR-TB), a form of tuberculosis (TB) resistant to two of the most powerful TB drugs, isoniazid and rifampicin.  Cure is only achieved in 50-60 percent of MDR-TB cases globally. Dr. Dalene von Delft’s diagnosis with MDR-TB was completely unexpected – she had what she believed to be a persistent dry cough and harmless sinusitis. Following MDR-TB diagnosis, Dalene underwent months of difficult treatment where she stomached 35 pills a day and endured painful daily injections. One of the injectable drugs in Dalene’s regimen was damaging her hearing and threatening to silence her world, a side effect that Dalene and her husband were unwilling to accept. They needed a replacement drug, but chronic under-investment in TB drug development left them to choose among a limited suite of decades-old drugs carrying high toxicities.

MDR-TB Behind the Numbers: Drs. Dalene and Arne von Delft from Visual Epidemiology on Vimeo.
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Declaration of the Global Chagas Disease Coalition

Chagas disease is a silent killer. Throughout the Americas, an estimated 8-10 million people, most of whom are predominantly poor and marginalized, are infected by the deadly parasite causing Chagas disease, Trypanosoma cruzi. Children are particularly affected. With globalization, the disease is increasingly found in the US, Europe, Australia, and Japan. The US is now the seventh most affected nation worldwide. Tens of thousands of patients die each year from Chagas disease. About 30% of chronically infected individuals will develop heart complications with high probability of death. Less than 0.2% receive treatment today (DNDi, unpublished data). New problems are emerging notably with mother-to-child transmission, which could become the new face of Chagas disease.

Chagas disease is a hidden public health crisis needing increased and urgent attention.
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This Week in PLOS NTDs and PLOS Pathogens: Chagas in North America, T Cells, Antibodies and Protective Immunity Against Dengue, a Closer Look at Bat-transmitted Viruses, and More

The following new articles are publishing this week in PLOS NTDs:

Arnott A, Mueller I, Ramsland PA, Siba PM, Reeder JC, et al. (2013). PLoS Negl Trop Dis 7(10): e2506. doi:10.1371/journal.pntd.0002506

Arnott A, Mueller I, Ramsland PA, Siba PM, Reeder JC, et al. (2013). PLoS Negl Trop Dis 7(10): e2506. doi:10.1371/journal.pntd.0002506

The poorest people living in the Mexico and the U.S. are silently suffering under a heavy burden of Chagas disease, with pregnant women disproportionately affected. Peter Hotez and colleagues discuss how many lives can be saved with greater access to the treatments available today, while knowing the fate of tomorrow’s patients rests on increasing investments in research to develop new technologies to treat and diagnose Chagas disease, as well as improving scientific cooperation between the U.S., Canada, Mexico, and other key countries.

Vaccines are an essential component of global malaria control and elimination campaigns, but the diversity of malaria antigens is thought to be a major cause of vaccine failure. In this study, Alicia Arnott and colleagues investigate the global diversity of the P. vivax vaccine candidate, Apical Membrane Antigen 1 (PvAMA1), to determine the feasibility of designing a globally effective PvAMA1 vaccine and to determine which region of PvAMA1 is targeted by host immune responses, in order to identify the most promising candidates.
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